, Volume 57, Issue 3, pp 273–277 | Cite as

Behavioral supersensitivity to apomorphine following chronic narcotic treatment in the guinea pig

  • Kristin R. Carlson
  • John Almasi


Male albino guinea pigs were treated for 3 weeks with methadone, morphine, haloperidol, or saline. One week and 5 weeks following termination of treatment they were challenged with the directly acting dopaminergic agonist apomorphine. At the week 1 test the haloperidol and saline groups did not differ, but behavioral supersensitivity was apparent in significantly elevated mean stereotypy scores of the methadone and morphine groups relative to the saline group. The source of differences in mean scores was a higher peak score rather than increased duration of action. At the week 5 test the scores of the methadone group were even higher, the morphine group's scores were equivalent to the saline group's, and the haloperidol group's scores were significantly depressed. This study indicates that a 3-week treatment period with methadone or morphine is sufficient to induce dopaminergic supersensitivity and suggests that there may be different time courses for the retention or expression of supersensitivity following these narcotics.

Key words

Apomorphine Methadone Morphine Haloperidol Guinea pig Dopamine Supersensitivity Stereotypies Tardive dyskinesia Narcotics 


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  1. Ahtee, L.: Catalepsy and stereotypies in rats treated with methadone: relation to striatal dopamine. Eur. J. Pharmacol. 27, 221–230 (1974)Google Scholar
  2. Andén, N.-E., Rubenson, A., Fuxe, K., Hokfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)Google Scholar
  3. Carlson, K. R., Almasi, J.: Sensitivity to apomorphine in the guinea pig as a function of age and body weight. Psychopharmacology 57, 279–282 (1978)Google Scholar
  4. Carlson, K. R., Eibergen, R. D.: Susceptibility to amphetamine-elicited dyskinesias following chronic methadone treatment in monkeys. Ann. N. Y. Acad. Sci. 281, 336–349 (1976)Google Scholar
  5. Costall, B., Naylor, R. J.: On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia (Berl.) 34, 233–241 (1974)Google Scholar
  6. Crane, G. E., Paulson, G.: Involuntary movements in a sample of chronic mental patients and their relation to the treatment with neuroleptics. Int. J. Neuropsychiatry 3, 286–291 (1967)Google Scholar
  7. Creese, I., Burt, D. R., Snyder, S. H.: Dopamine receptor binding predicts clinical and pharmacological potencies of antischizoprenic drugs. Science 192, 481–483 (1976)Google Scholar
  8. Eibergen, R. D., Carlson, K. R.: Behavioral evidence for dopaminergic supersensitivity following chronic treatment with methadone or chlorpromazine in the guinea pig. Psychopharmacology 48, 139–146 (1976a)Google Scholar
  9. Eibergen, R. D., Carlson, K. R.: Dyskinesias in monkeys: interaction of methamphetamine with prior methadone treatment. Pharmacol. Biochem. Behav. 5, 175–187 (1976b)Google Scholar
  10. Eidelberg, E., Erspamer, R.: Dopaminergic mechanisms of opiate actions in brain. J. Pharmacol. Exp. Ther. 192, 50–57 (1975)Google Scholar
  11. Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)Google Scholar
  12. Fjalland, B., Moller-Nielsen, I.: Enhancement of methylphenidate-induced stereotypies by repeated administration of neuroleptics. Psychopharmacologia (Berl.) 34, 105–109 (1974)Google Scholar
  13. Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)Google Scholar
  14. Gianutsos, G., Hynes, M. D., Puri, S. K., Drawbaugh, R. B., Lal, H.: Effect of apomorphine and nigrostriatal lesions on aggression and striatal dopamine turnover during morphine with-drawal: evidence for dopaminergic supersensitivity in protracted abstinence. Psychopharmacologia (Berl.) 34, 37–44 (1974)Google Scholar
  15. Klawans, H. L., Jr., Rubovits, R.: An experimental model of tardive dyskinesia. J. Neural Trans. 33, 235–246 (1972)Google Scholar
  16. Kreek, M. J., Gutjahr, C. L., Garfield, J. W., Bowen, D. V., Field, F. H.: Drug interactions with methadone. Ann. N. Y. Acad. Sci. 281, 350–371 (1976)Google Scholar
  17. Lal, S., Feldmuller, F.: Effect of amphetamine and apomorphine on brain monoamines and behavior in the immature and young adult rat. Arch. Int. Pharmacodyn. 218, 239–251 (1975)Google Scholar
  18. Moffett, A. D., Soloway, I. H., Glick, M. X.: Post-treatment behavior following ambulatory detoxification. In: Methadone: experiences and issues, C. D. Chambers and L. Brill, eds., pp. 215–227. New York: Behavioral Publications 1973Google Scholar
  19. Perez-Cruet, J., Di Chiara, G., Gessa, G. L.: Accelerated synthesis of dopamine in the rat brain after methadone. Experientia 28, 926 (1972)Google Scholar
  20. Puri, S. K., Lal, H.: Effect of dopaminergic stimulation or blockade on morphine-withdrawal aggression. Psychopharmacologia (Berl.) 32, 113–120 (1973)Google Scholar
  21. Puri, S. K., Reddy, C., Lal, H.: Blockade of central dopaminergic receptors by morphine: effect of haloperidol, apomorphine or benztropine. Res. Commun. Chem. Path. Pharmacol. 5, 389–401 (1973)Google Scholar
  22. Sasame, H. A., Perez-Cruet, J., Di Chiara, G., Tagliamonte, A., Tagliamonte, P., Gessa, G. L.: Evidence that methadone blocks dopamine receptors in the brain. J. Neurochem. 19, 1953–1957 (1972)Google Scholar
  23. Sayers, A. C., Burki, H. R., Ruch, W., Asper, H.: Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of clozapine, haloperidol, loxapine and chlorpromazine. Psychopharmacologia (Berl.) 41, 97–104 (1975)Google Scholar
  24. Srimal, R. C., Dhawan, B. N.: An analysis of methylphenidate induced gnawing in guinea pigs. Psychopharmacologia (Berl.) 18, 99–107 (1970)Google Scholar
  25. Tarsy, D., Baldessarini, R. J.: Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13, 927–940 (1974)Google Scholar
  26. Tarsy, D., Baldessarini, R. J.: The tardive dyskinesia syndrome. In: Clinical neuropharmacology, vol. 1, H. L. Klawans Jr., ed., pp. 29–61. New York: Raven Press 1976Google Scholar
  27. Teiger, D. G.: A test for antinociceptive activity of narcotic and narcotic antagonist analgesics in the guinea pig. J. Pharm. Exp. Ther. 197, 311–316 (1976)Google Scholar
  28. Ungerstedt, U., Butcher, L. L., Butcher, S. G., Andén, N.-E., Fuxe, K.: Direct chemical stimulation of dopaminergic mechanisms in the neostriatum of the rat. Brain Res. 14, 461–471 (1969)Google Scholar
  29. Winer, B. J.: Statistical principles in experimental design, 2nd ed. New York: McGraw-Hill 1971Google Scholar
  30. York, D. H.: Dopamine receptor blockade—a central action of chlorpromazine on striatal neurons. Brain Res. 37, 91–99 (1972)Google Scholar

Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • Kristin R. Carlson
    • 1
  • John Almasi
    • 1
  1. 1.Department of PharmacologyUniversity of Pittsburgh School of MedicinePittsburghUSA

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